Orodispersible dosage unit containing an estetrol component
The invention provides an orodispersible solid pharmaceutical dosage unit having a weight between 30 and 1,000 mg, said dosage unit consisting of: 0.1-25 wt. % of estetrol particles containing at least 80 wt. % of an estetrol component selected from estetrol, estetrol esters and combinations thereof; and 75-99.9 wt. % of one or more pharmaceutically acceptable ingredients; the solid dosage unit comprising at least 100 μg of the estetrol component; and wherein the solid dosage unit can be obtained by a process comprising wet granulation of estetrol particles having a volume weighted average particle size of 2 μm to 50 μm. The solid dosage unit is easy to manufacture and perfectly suited for sublingual, buccal or sublabial administration.
1. A solid pharmaceutical dosage unit having a weight of 30 to 1,000 mg, the dosage unit consisting of:
0.1-30 wt. % of estetrol particles having a volume median diameter of 2 μm to 50 μm, containing at least 90 wt. % of an estetrol component selected from estetrol, estetrol esters, and combinations thereof, and being present in the dosage unit as a component of dry estetrol-containing granules that further comprise one or more granulation excipients; and
70-99.9 wt. % of one or more pharmaceutically acceptable ingredients;
the solid dosage unit comprising at least 100 μg of the estetrol component.
2. The solid pharmaceutical dosage unit according to claim 1 , wherein the dosage unit comprises the estetrol component in an amount of at least 1 wt. %.
3. The solid pharmaceutical dosage unit according to claim 1 , wherein the estetrol particles have a volume median diameter of 3 μm to 35 μm.
4. The solid pharmaceutical dosage unit according to claim 1 , wherein the estetrol-containing granules comprise the one or more granulation excipients in an amount of 70-95 wt. % and the estetrol component in an amount of 5-30 wt. % of the estetrol component.
5. The solid pharmaceutical dosage unit according to claim 1 , wherein the dosage unit is an orodispersible solid pharmaceutical dosage unit.
6. The solid pharmaceutical dosage unit according to claim 5 , wherein the dosage unit has a disintegration time in water of less than 5 minutes.
7. The solid pharmaceutical dosage unit according to claim 6 , wherein the dosage unit has a disintegration time in water of less than 2 minutes.
8. The solid pharmaceutical dosage unit according to claim 6 , wherein the disintegration time is determined by a disintegration test according to Ph. Eur. 2.9.1. or USP<701>.
9. The solid pharmaceutical dosage unit according to claim 1 , wherein the estetrol component is estetrol or an ester thereof.
10. The solid pharmaceutical dosage unit according to claim 1 , wherein the dosage unit is a tablet, dragée, lozenge, or film.
11. The solid pharmaceutical dosage unit according to claim 10 , wherein the dosage unit is a tablet.
12. The solid pharmaceutical dosage unit according to claim 1 , wherein the pharmaceutically acceptable ingredient comprises a progestin selected from the group consisting of: progesterone, desogestrel, etonogestrel, gestodene, dienogest, levonorgestrel, norgestimate, norethisterone, norethisteron-acetate (NETA), nomegestrol, nomegestrol-acetate (NOMAC), drospirenone, trimegestone, nestorone, and dydrogesterone.
13. The solid pharmaceutical dosage unit according to claim 12 , wherein the progestin is 0.05-10 mg of drospirenone.
14. The solid pharmaceutical dosage unit according to claim 1 , wherein the dosage unit is formed by a process comprising direct compression or compression moulding.
15. The solid pharmaceutical dosage unit according to claim 1 , wherein the dosage unit releases at least 70% of the estetrol component after 5 minutes in an aqueous dissolution medium.
16. The solid pharmaceutical dosage unit according to claim 15 , wherein the dosage unit releases at least 80% of the estetrol component after 5 minutes in an aqueous dissolution medium.
17. A method of providing female hormone replacement therapy to a subject in need thereof, comprising administering a solid dosage unit according to claim 1 by sublingual, buccal or sublabial administration.
18. The method of claim 17 , wherein the administering is by once daily administration during a period of at least 1 week.
19. A method of providing female contraception to a subject in need thereof, comprising administering a solid dosage unit according to claim 1 by sublingual, buccal or sublabial administration.
20. The method of claim 19 , wherein the administering is by once daily administration during a period of at least 1 week.